Table 2.
Receptor–ligand interaction of six phenolic acids docking with JAKs.
| Ligand | Docking Receptor | Closest Distance to Met 956 | Hydrogen Bond the Hinge Region (Length: Å) |
Hydrogen Bond N- and C-Terminal Lobes (Length: Å) |
Hydrophobic Contacts | π-Interactions (π-Cation and π-π Stacking) |
|---|---|---|---|---|---|---|
| RosA | 6DBN | 4.324 | L959 (3.11) | K908 (3.912) | V889 | K908 |
| S963 (3.759) | L1010 | (π-cation) | ||||
| CY | 6DBN | 2.952 | L959 (3.829) | R879 (2.955) | L881 | K908 |
| G1020 (2.662) | G962 | (π-cation) | ||||
| SalA | 6DBN | 3.716 | L959 (3.391) | R879 (2.979) | L881 | - |
| E883 (2.009) | G962 | |||||
| SalC | 6DBN | 3.77 | L959 (2.782) | R879 (3.074) | L881 | K908 |
| R1007 (2.060) | G884 | (π-cation) | ||||
| K908 (3.300) | G962 | |||||
| L1010 | ||||||
| LSA | 6DBN | 4.179 | L959 (3.074) | R879 (2.995) | L881 | K908 |
| G1020 (2.182) | G962 | (π-cation) | ||||
| SalB | 6DBN | 4.187 | L959 (2.341) | G884 (2.328) | V889 | F886 (π-π) |
| H885 (2.080) | L1010 | |||||
| K908 (3.379) | ||||||
| R1007 (3.621) | ||||||
| N1008 (3.077) | ||||||
| D1042 (1.966) | ||||||
| SalC | 3EYG | 3.849 | L959 (3.050) | R879 (3.943) | L1010 | - |
| L881 (2.068) | A906 | |||||
| E883 (2.359) | L881 | |||||
| S963 (3.672) | V889 | |||||
| G962 | ||||||
| CY | 3EYG | 2.828 | L959 (2.967) | R879 (3.052) | L1010 | - |
| L881 (2.704) | V889 | |||||
| G962 | ||||||
| SalB | 3EYG | 4.237 | F958 (2.490) | K908 (3.158) | V889 | - |
| S963 (3.799) | L1010 | |||||
| R1007 (2.512) | G882 | |||||
| D880 (3.056) | ||||||
| E883 (3.086) |
1. Hydrogen bonds and bond lengths between ligands and receptors were analyzed using UCSF Chimera; π-interactions and hydrophobic contacts were analyzed using PoseView. 2. The gatekeeper residue Met 956 on the ATP binding pocket limits the acceptable ligand volume [31]. Due to the flexible structure, the configuration of these six phenolic acids in docking can be very close to Met956, and the distances are recorded in the table (unit: Å). 3. According to Williams, NK et al., the protein tyrosine kinases (PTKs) domains of JAK1/2 include (1) an N-terminal lobe (residues 865–955) with 5 β-sheets and 1 α-helix; and (2) C-terminal lobe (residues 960–1154) with eight α-helices. Between the two lobes is the substrate (ATP)-binding cleft. The hinge region (Met956, Glu957, Phe958, Leu959) is bounded between the N-terminal and C-terminal lobes [25]. The most important interaction between Tofacitinib and JAK is the two hydrogen bonds of Leu959 and Glu957. Hydrogen bonds to the hinge region are of relative importance and are therefore listed separately.